Review article: Chemokine production by intestinal epithelial cells: a therapeutic target in inflammatory bowel disease?
The intestinal epithelium plays an important role in the recognition of pathogenic organisms and in the recruitment of inflammatory cells to the mucosa. Epithelial chemokine production may constitute a key target in future therapies for inflammatory bowel disease (IBD). Chemokines are divided into two subfamilies, the C-C family and C-X-C family. Most C-C chemokines target mononuclear cells and many C-X-C chemokines attract neutrophils. Interleukin-8 (IL-8), a C-X-C chemokine, acts as a motor for the recruitment of neutrophils into the non-inflamed mucosa and is present in both enterocytes and mucosal inflammatory cells. Epithelial cells may be the first to signal the presence of pathogens, as well as contributing to IL-8 production in IBD. Data have also shown that intestinal epithelial cells are able to respond to IL-1 and tumour necrosis factor-alpha (TNF-alpha) at concentrations known to occur in the inflamed mucosa. Monocyte chemotactic protein-1 (MCP-1), a member of the C-C chemokine family, is noticeably increased in IBD. These data show that C-X-C and C-C chemokines are equally important properties of mucosal epithelial cells. The effects of two anti-inflammatory drugs (dexamethasone and cyclosporin) on chemokine production are significantly different and this provides a rationale for combination therapy.
van Deventer
S J
SJ
Laboratory for Experimental Internal Medicine, Academic Medical Centre, Amsterdam, The Netherlands.
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D019742:Chemokines, CC / Q000096:biosynthesis*; D019743:Chemokines, CXC / Q000096:biosynthesis*; D016572:Cyclosporine / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D018375:Neutrophil Activation
D000893:Anti-Inflammatory Agents; D019742:Chemokines, CC; D019743:Chemokines, CXC; D007166:Immunosuppressive Agents; D003907:Dexamethasone; D016572:Cyclosporine